EHNS/ESMO/ESTRO

Locally advanced disease, induction

Note that these regimens are intended to be followed by definitive radiotherapy or chemoradiotherapy. In some circumstances, treatment may be followed by surgery; if this sequence was pre-planned it would be considered a neoadjuvant approach as opposed to an induction approach.

Subsequent treatment

Patients with CR or PR of greater than 80% in the primary tumor and no evidence of progression in neck lymph nodes: Definitive cisplatin & RT

Patients with a PR of less than 80% or stable disease in the neck lymph nodes (especially if N2 or N3 disease) after induction: Neck dissection, if the surgeons were in agreement, before the administration of adjuvant chemoradiotherapy

Patients with no response or progression of disease were taken off study

GORTEC 2000-01: re-evaluation is performed

Patients who responded to induction chemotherapy: Definitive RT within 3 to 7 weeks of finishing chemotherapy

Patients who did not respond to induction chemotherapy: Surgery, then adjuvant RT (see Pointreau et al. 2009 for details)

Supportive medications

Prophylactic G-CSF only allowed for patients who had "febrile neutropenia or infection, a delay in recovery of the absolute neutrophil count at day 28, or grade 4 neutropenia persisting for 7 days or more."

21-day cycle for 4 cycles

Subsequent treatment

EORTC 24971/TAX 323: Patients without progressive disease and who had recovery of marrow function, resolution of mucositis, and healed from any dental procedures started definitive RT within 4 to 7 weeks of finishing chemotherapy

Patients with CR or PR of greater than 80% in the primary tumor and no evidence of progression in neck lymph nodes: Definitive cisplatin & RT

Patients with a PR of less than 80% or SD in the neck lymph nodes (especially if N2 or N3 disease) after induction CT: Neck dissection, "if the surgeons were in agreement, before the administration of CRT."

Patients with no response or progression of disease were taken off study

Prophylactic granulocyte colony-stimulating factor only allowed for patients who had "febrile neutropenia or infection, a delay in recovery of the absolute neutrophil count at day 28, or grade 4 neutropenia persisting for 7 days or more."

21-day cycle for 4 cycles

Subsequent treatment

Patients without progressive disease and who had recovery of marrow function, resolution of mucositis, and healed from any dental procedures started definitive RT within 4 to 7 weeks of finishing chemotherapy

Subsequent treatment

Patients who had an initial nodal stage of N2 and a partial response to induction chemotherapy, N3 disease, or residual disease after chemoradiotherapy: Surgery, 6 to 12 weeks after completion of chemoradiotherapy

Supportive medications

Best described by Al-Sarraf et al. 1998

Forced hydration: 5% dextrose in 1/2 normal saline with 40 mEq KCl, 2000 mL IV continuous infusion over 24 hours given twice, before each dose of Cisplatin (Platinol) and after the second mannitol infusion

This is included for historical context and is unlikely to be further completed. Efficacy for Gollin et al. 1972 is based on the 1976 update, for oral lesions only. Efficacy in Merlano et al. 1992 is based on the 1995 update.

Preceding treatment

Chemoradiotherapy

Concurrent radiation therapy, 1.7 Gy fractions x ~32 fractions (total dose: 54 Gy), given 5 times per week, with boost to "primary site and/or cervical lymph nodes" with 1.8 to 2 Gy fractions for an additional boost dose of 11 to 16 Gy to close (<5 mm) or positive margin areas of (overall dose to these sites: 65 to 70 Gy). A boost of 11 to 20 Gy was given to metastatic nodal sites (overall dose to these sites: 65 to 74 Gy); see Bachaud et al. 1996 for details.

Chemotherapy

ECOG E1395: Carboplatin AUC 6 IV once on day 1 could be substituted in patients who developed at least grade 2 neuropathy or renal impairment (CrCl less than 50 mL/min/1.73m2; note: later in Gibson et al. 2005, it says that carboplatin was used for patients who had CrCl less than or equal to 50 mL/min/1.73m2)

In Clavel et al. 1994, patients proceeded to cisplatin monotherapy after 3 cycles. In ECOG E1395, patients with complete response (CR) received at least 6 cycles or 2 cycles past the point at which CR was documented, whichever came later; patients with partial response (PR) continued on treatment until there was evidence of CR or progression disease; patients with stable disease (SD) could discontinue treatment after six cycles.

Variant #5, 100 mg/m2 q4wk

Chemotherapy

Per physician discretion, patients with complete response (CR) could have treatment discontinued 2 cycles past the point at which CR was attained. Patients with partial response (PR) continued on treatment until there was evidence of CR or progression disease. Patients with stable disease (SD) could discontinue treatment after 6 cycles. Patients with progressive disease discontinued therapy.

Cisplatin & Cetuximab

Regimen

Chemotherapy

Cycle 1: 200 mg/m2 IV over 2 hours once on day 1, then 125 mg/m2 IV over 60 minutes once per day on days 8, 15, 22

Subsequent cycles: 125 mg/m2 IV over 60 minutes once per day on days 1, 8, 15, 22

28-day cycles

Per physician discretion, patients with complete response (CR) could have treatment discontinued 2 cycles past the point at which CR was attained. Patients with partial response (PR) continued on treatment until there was evidence of CR or progression disease. Patients with stable disease (SD) could discontinue treatment after 6 cycles. Patients with progressive disease discontinued therapy.

Cisplatin & Paclitaxel

Regimen

Chemotherapy

Carboplatin AUC 6 IV once on day 1 could be used in patients who developed at least grade 2 neuropathy or renal impairment (CrCl less than 50 mL/min/1.73m2; note: later in Gibson et al. 2005, it says that carboplatin was used for patients who had CrCl less than or equal to 50 mL/min/1.73m2)

Patients with complete response (CR) received at least 6 cycles or 2 cycles past the point at which CR was documented, whichever came later. Patients with partial response (PR) continued on treatment until there was evidence of CR or progression disease. "Patients with stable disease (SD) could discontinue treatment after six cycles."

Cetuximab monotherapy

Regimen

Note: Vermorken et al. 2007 gave a 20 mg test dose as part of the initial dose; this is not specified in CheckMate 141. To our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.

Chemotherapy

Cetuximab (Erbitux) 400 mg/m2 IV over 2 hours once on day 1, then 250 mg/m2 IV over 60 minutes once per week